Combating animal acarid ectoparasites with 2-phenyliminopyrrolidines

ABSTRACT

2-PHENYLIMINOPYRROLIDINES, I.E. 1-(ALKYL AND ALKENYL)2-(DI AND (TRI(HALO AND ALKYL SUBSTITUTED)-PHENYLIMINO)(OPTIONALLY 3-, 4- OR 5 - ALKYL SUBSTITUTED-PYRROLIDINES, WHICH POSSESS PARASITICIDAL PROPERTIES, ESPECIALLY ANIMAL ACARID ECTOPARASITICAL PROPERTIES, AND WHICH MAY BE PRODUCED BY CONVENTIONAL METHODS.

United States Patent ()flice 3,787,576 COMBATING ANIMAL ACARID ECTOPARASITES WITH Z-PHENYLIMINOPYRROLIDINES Edgar Enders, Cologne-Flittard, and Wilhelm Stendel, Wuppertal-Vohwinkel, Germany, assignors to Bayer Aktiengesellschaft, Leverkusen, Germany No Drawing. Original application June 18, 1969, Ser. No. 834,537, now abandoned. Divided and this application June 9, 1971, Ser. No. 151,516

Int. Cl. A01n 9/22 US. Cl. 424-274 6 Claims ABSTRACT OF THE DISCLOSURE 2-phenyliminopyrrolidines, i.e. l-[alkyl and alkenyl]- 2-[di and tri(halo and alkyl substituted)-phenylimino]- [optionally 3-, 4- or 5 allyl substituted]-pyrrolidines, which possess parasiticidal properties, especially animal acarid ectoparasiticidal properties, and which may be produced by conventional methods.

This application is a division of US. patent application Ser. No. 834,537, filed June 18, 1969, now abandoned.

The present invention relates to and has for its objects the provision for particular new 2 phenyliminopyrrolidines, i.e. l-[alkyl and alkenyl] -2- [di and tri(halo and alkyl substituted) phenylimido] [optionally 3-, 4- or 5- alkyl substituted]-pyrrolidines, which possess parasiticidal, especially animal acarid estoparasiticidal properties, active compositions in the form of mixtures of such compounds with solid and liquid dispersible carrier vehicles, and methods for producing such compounds and for using such compounds in a new way especially for combating pests, e.g. parasites, especially animal acarid estoparasites, with other and further objects becoming apparent from a study of the within specification and accompanying examples.

No phenylimino-pyrrolidines of the type contemplated by the present invention have been heretofore described in the literature, and certainly no such compounds have been suggested as having parasiticidal activity.

It has been found, in accordance with the present invention, that the particular new 2-phenylimino-pyrrolidines of the formula in which R is chloro, bromo, fiuoro or alkyl of l-4 carbon atoms,

n is a whole number from 2-3,

with the proviso that at least one of the substituents R is chloro, bromo or fiuoro,

R is alkyl of 1-6 or 2-6 carbon atoms, or alkenyl of 3-4 carbon atoms, and

R" is hdrogen or alkyl of 1-4 carbon atoms,

exhibit strong pesticid-al, especially animal acarid ecoparasiticidal, properties.

It has been furthermore found, in accordance with the present invention, that the compounds of Formula I above 3,787,576 Patented Jan. 22, 1974 may be produced by the proces which comprises condensing an aniline of the formula in which R and n are the same as defined above, with a pyrrolidone of the formula in which R is alkyl of 1-6 or 2-6 carbon atoms, or alkenyl of 3-4 carbon atoms, and R" is the same as defined above, in the presence of an agent which splits off water, and isolating the product thereby produced in the form of the corresponding halogen hydracid salt or in free form and, optionally, then converting the same into any other desired salt.

Advantageously, the particularly new compounds of Formula I are distinguished by outstanding animal acarid ectoparasiticidal properties, especially against resistant strains of such parasites as well as extremely low toxicity to warm-blooded animals. In contrast thereto, the previously known phosphoric acid esters and carbamates used to combat such parasites, are less effective because resistance builds up in initially susceptible parasites of the foregoing kind to such known compounds. The new compounds of the present invention therefore represent a genuine enrichment of the art.

If 3,4-dichloro-aniline and N-butyl-pyrrolidone(2) are used as starting materials, the reaction course can be represented by the following formula scheme:

( Ia) (IIIa) Advantageously, in accordance with the present inven tion, in the various formulae herein:

R represents chloro; bromo; fluoro; and/or straight and branched chain lower'alkyl of 1-4 carbon atoms such as methyl, ethyl, nand iso-propyl, n-, iso-, sec.- and tert.-butyl, and the like, especially C or C alkyl, and more especially methyl and ethyl;

n represents a whole number from 2 to 3, especially 2;

with the proviso that at least one of the substituents R R represents straight and branched chain alkyl hydrocarbon of 1-6 carbon atoms such as methyl to tert.-butyl inclusive as defined above, amyl, n-hexyl, pinacolyl (i.e. [CH C[CH ]CH-), and the like, especially C or C alkyl; or straight and branched chain alkenyl hydrocarbon of 3 to 4 carbon atoms such as w, 5- and 'y-allyl (i.e. prop-1 and Z-enyl and l-methylvinyl), but-1,2 and 3-enyl, and the like, especially w allyl and but-Z-enyl; and

R" represents hydrogen; or straight and branched chain lower alkyl hydrocarbon of 1-4 carbon atoms such as methyl to tert.-butyl inclusive as defined above, and the like, especially C or C alkyl, more especially S-position substituted C or C alkyl, and most especially methyl.

Preferably, R is dichloro, trichloro, dibrorno, (C alkyl)-(chloro), (C alkyl)-(bromo), chloro-bromo, chloro-fluoro, or bromo-fluoro; R is C alkyl, or C alkenyl; and R is hydrogen, or C or C alkyl.

In particular, R is 2,3-, 2,4-, 2,5- and 3,4-dichloro, 2,4,5-trichloro, 2,4- and 3,4-dibromo, 2-chloro-4-bromo, 2-bromo-4-chloro, 3-chloro-4-bromo, 3-bromo-4-chloro, 2-chloro-4-fiuoro, 3-chloro-4-fluro, 2-methy1-4-chloro, 3- methyl-4-chloro, 3-chloro-4-methyl, 2-bromo-4-fluoro, 3- bromo-4-fiuoro, 2-methyl-4-bromo, and 2-ethyl-4-bromo.

The aniline starting materials of Formula II above are known.

As examples of preferred anilines usable as starting materials herein, there are mentioned:

2,4-dichloro-aniline 3,4-dichloro-aniline 2,4,5-trichloro-aniline 2,4,6-trichloro-aniline 3,4,5-trich1oro-aniline 2,3,4-trichloro-aniline 4-chloro-2-methyl-aniline 2-chloro-4-methyl-aniline 2,4-dichloro-5-methyl-aniline 2,4-difluoro-aniline 4-fluoro-2-chloro-aniline 4-chloro-2-fiuoro-aniline 4-chloro-2-ethyl-aniline 4-fluoro-3-chloro-aniline 2,4-difluoro-5-chloro-aniline 4-fluoro-2-methyl-aniline 2-chloro-4-bromo-aniline 4-chloro-2-bromo-aniline 2,4-dibromo-aniline 4-bromo-2-methyl-aniline 4-fluoro-2-bromo-aniline 2,S-dichloro-4-bromo-aniline 4,5-dichloro-2-bromo-aniline 2-fiuoro-4-bromo-aniline 4-bromo-2-ethyl-aniline 4-bromo-2-isopropyl-aniline The pyrrolidones of Formula III above usable as starting materials are also known.

Pyrrolidones which are suitable for the production process according to the present invention, include in particular:

N-ethyl-pyrrolidone-(Z) N-n-propyl-pyrrolidone-(2) N-isopropyl-pyrrolidone-(2) N-allyl-pyrrolidone-(2) N-n-butyl-pyrrolidone-(Z) N-sec.-butyl-pyrrolidone-(2) N-tert.-butyl-pyrrolidone-(2) N-isobutyl-pyrrolidone-(2) N-n-pentyl-pyrrolidone-(2) N-n-hexyl-pyrrolidone-(2) I-S-dimethyl-pyrrolidone-(2) l-ethyl-S -methyl-pyrrolidone-( 2) l-propyl-S-rnethyl-pyrrolidone-(2) 1,3-diinethyl-pyrrolidone-(2) N-crotyl-pyrrolidone-(Z) N-methylallyl-pyrrolidone- (2) N-(buten-(3)-yl)-pyrrolidone-(2) The production reaction can be carried out, if desired, in the presence of an inert solvent (the term solvent including mere diluents). Suitable solvents are aromatic hydrocarbons, such as benzene, toluene and xylene, and chlorinated hydrocarbons, such as chlorobenzene, d1- chlorobenzenes and tetrachloroethylene, and the like.

As agents which split off water, inorganic acid halides are preferably used, such as phosphorus oxychloride, thiophosphoryl chloride, phosphorus trichloride, thionyl chloride, phosgene, silicon tetrachloride, stannous tetrachloride, and the like.

The reaction temperatures which may be used can be varied advantageously within a fairly wide range. In general, the reaction is carried out at substantially between about 10130 0, preferably from about 20-120 C.

When carrying out the instant production process, the two starting materials are normally used in about equimolar amounts and an equimolar amount of the agent which splits ofi water is added.

In general, all the reactants are added together and only then is the reaction mixture heated to higher temperatures, for example -120 C. The reaction is complete when the evolution of halogen hydride has ceased.

The instant 2-phenylimino-pyrrolidines are obtained as halogen hydracid salts which are sparingly soluble in organic solvents. The compounds can be isolated as such.

For purification, the instant free bases can be liberated by treatment with an aqueous solution of sodium hydroxide or of potassium hydroxide and then distilled.

Advantageously, the instant free bases can be reacted with the appropriate acids to produce any desired salt, for example with inorganic acids, such as sulfuric acid, hydrochloric acid, phosphoric acid, or with organic acids, such as acetic acid, tartaric acid, citric acid, benzenesulfonic acid, and the like.

Advantageously, the instant Z-phenylimino-pyrrolidines and their corresponding salts exhibit strong acaricidal properties, particularly against acarids which as animal ectoparasites infest domesticated animals or live stock such as cattle, sheep, rabbits, and the like. At the same time, the instant active compounds show only a low toxicity to warm-blooded animals. Such compounds are therefore well suited for the control of acarid animal ectoparasites.

As economically important ectoparasites of this nature contemplated herein, particularly in tropical and subtropical countries, there are mentioned for example: the Australian and South American cattle tick Boophilus microplus, the South African cattle tick Boophilus decolaratus, both of the family of the Ixodidae, and the like. In the same manner, representatives of the Sarcoptidae family such as the rabbit sucking-mite (Paoropt es cuniculi), and the like, can also be controlled.

Further ectoparasites of the order Acarida with great economical importance, which live in the Tropics, Subtropics or in the temperate zones, are for example:

From the family Ixodidae: The single host cattle tick of Central American, Boophilus annulatus; the multihost brown-ear-tick of sheep and cattle, Rhzpicephalus appendiculams; the red-legged tick of sheep and cattle, Rhipicephalus evertsi; the bout tick of sheep and cattle, Amblyomma hebraeum; the bout-legged tick, Hyalomma truncatum.

From the family Sarcoptidae: The sheep-scab mite Psoroptes ovis.

From the family Dermanyssidae: The red-poultry mite Dermanyssus 'gallinae.

The compounds according to the present invention show surprisingly a high activity not only against the single host ticks, for instance the above-mentioned ticks of that type, but also against the multihost ticks, for instance the above-mentioned ticks of that type.

In the course of time, ticks in particular have become resistant against the known phosphoric acid esters and carbamates hitherto used as active agents, for their control, so that successful control in many areas is becoming more and more doubtful. To secure economic cattle husbandry in the infestation areas, there exists an urgent need for active agents which can control all development stages, that is larvae, nymphs, metanymphs, and adults, even of resistant strains, for example of the genus Boophilus. In this regard, up to now in Australia, for instance, the Ridgeland strain and the Biarra strain of Baophilus microplus are resistant to a great extent against the appropriate known phosphoric acid ester active agents.

The active compounds according to the present invention are equally effective against the normally sensitive, as well as the resistant, strains, for example of Boophilus. Such active compounds act, on the usual application to the host animal, not only directly lethally on all forms parasitic on the animal but also strongly ovicidally on the adult forms, so that the propagation cycle of the ticks is interrupted both in the parasitic phase on the animal and in the non-parasitic phase. Thus, the laying of eggs is substantially prevented, and the development and hatching of eggs are inhibited.

The active compounds according to the instant invention can be utilized, if desired, in the form of the usual formulations or compositions with inert conventional pesticidal diluents or extenders, i.e. conventional pesticidal dispersible carrier vehicles, such as solutions, emulsions, suspension, emulsifiable concentrates, spray powders, pastes, soluble powders, dusting agents, granules, etc. These are prepared in known manner, for instance by extending the active compounds with conventional pesticidal dispersible liquid diluent carriers and/ or dispersible solid carriers optionally with the use of carrier vehicle assistants, e.g. conventional pesticidal surface-active agents, including emulsifying agents and/or dispersing agents, whereby, for example, in the case where water is used as diluent, organic solvents may be added as auxiliary solvents. The following may be chiefly considered for use as conventional carrier vehicles for'this purpose: inert dispersible liquid diluent carriers, including inert organic solvents, such as aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated, especially chlorinated, aromatic hydrocarbons (e.g. chlorobenzenes, such as o-dichlorobenzene, trichlorobenzene, etc.), paraffins (e.g. petroleum fractions), chlorinated aliphatic hydrocarbons (e.g. methylene chloride, etc.), alcohols (e.g. methanol, ethanol, propanol, butanol, etc.), amines (e.g. ethanolamine, etc.), ethers, ether-alcohols (e.g. glycol monomethyl ether, etc.), amides (e.g. dimethyl formamide, etc.), pyrrolidones (e.g. N-methyl-pyrrolidone-Z), sulfoxides (e.g. dimethyl sulfoxide, etc.), ketones (e.g. acetone, etc.) and/or water; as well as inert dispersible finely divided solid carriers, such as ground natural minerals (e.g. kaolins, alumina, silica, chalk, i.e. calcium carbonate, talc, kieselguhr, etc.) and ground synthetic minerals (e.g. highly dispersed silicic acid, silicates, e.g. alkali silicates, etc.); whereas the following may be chiefly considered for use as conventional carrier vehicle assistants, e.g. surface-active agents, for this purpose: emulsifying agents, such as non-ionic and/or anionic and/or cationic emulsifying agents (e.g. polyethylene oxide esters of fatty acids, polyethylene oxide ethers of fatty alcohols, alkyl sulfonates, aryl sulfonates, etc., and especially alkyl arylpolyglycol ethers, magnesium stearate, sodium oleate, quaternary ammonium salts of longer, e.g. C alkyl radicals, etc.); and/or dispersing agents, such as lignin, sulfite waste liquors, methyl cellulose, etc.

Such active compounds may be employed alone or in the form of mixtures with one another and/or with such solid and/ or liquid dispersible carrier vehicles and/ or with other known compatible active agents, especially hygiene control or disinfectant agents, such as other parasiticides, or acaricides, insecticides, fungicides, bactericides, etc., if desired, or in the form of particular dosage preparations for specific application made therefrom, such as solutions, emulsions, suspensions, powders, pastes, and granules which are thus ready for use.

As concerns commercially marketed preparations, these generally contemplate carrier composition mixtures in which the active compound is present in an amount substantially between about 01-95% by weight, and preferably 0.5-% by weight, of the mixture, whereas carrier composition mixtures suitable for direct application or animal, e.g. livestock, application generally contemplate those in which the active compound is present in an amount substantially between about 0.001-5%, preferably 0.01-1 by weight of the mixture. Thus, the present invention contemplates over-all compositions which comprise mixtures of a conventional dispersible carrier vehicle such as (1) a dispersible inert finely divided carrier solid, and/or (2) a dispersible carrier liquid such as an inert organic solvent and/ or water preferably including a surface-active effective amount of a carrier vehicle assistant, e.g. a surface-active agent, such as an emulsifying agent and/or a dispersing agent, and an amount of the active compound which is effective for the purpose in question and which is generally between about 0.00 l%, and preferably 0.0195%, by weight of the mixture.

It will be appreciated that the application concentrations are produced in connection with the above noted formulations normally by dilution with water. Furthermore, such concentrations can, according to the application form, be varied within a fairly wide range and are generally substantially between about 10 to 50,000 p.p.m. (g./g.), preferably between about to 10,000 p.p.m., i.e. 0.0015%, preferably 0.01l%, as aforesaid.

Advantageously, the aqueous solutions or emulsions of the instant active compounds possess a markedly good stability under practical conditions, so that, even after standing for long periods at a pH in the range of from 7-9, such compounds may remain effective, i.e. even for three months or longer.

In particular, the present invention contemplates methods of selectively killing, combating or controlling pests, e.g. parasites, i.e. animal acarid ectoparasites, which comprises applying to at least one of correspondingly (a) such animal acarid ectoparasites, and (b) the corresponding habitat, i.e. the locus to be protected, e.g. the animal or livestock, a correspondingly combative or toxic amount, i.e. animal acarid ectoparasiticidally effective amount of the particular active compound of the invention alone or together with a carrier vehicle as noted above. The instant formulations or compositions are applied in the usual manner, for instance by spraying, atomizing, scattering, dusting, watering, i.e. as a bath (dip), sprinkling, pouring, and the like.

It will be realized, of course, that the concentration of the particular active compound utilized in admixture with the carrier vehicle will depend upon the intended application. Therefore, in special cases it is possible to go above or below the aforementioned concentration ranges.

The unexpected superiority and outstanding activity of the particular new compounds of the present invention is illustrated, without limitation, by the following examples:

EXAMPLE 1 In-vitro test for ovicidal effect on ticks 3 g. of the particular active compound are mixed with 7 g. of a mixture of equal parts by weight of ethylenecidal effect of the particular active compounds in accord ance with the present invention.

TABLE 1a.IN-VITRO TES IEOFIEJSR OVICIDAL EFFECT ON Active compound: l-methyl-2-(2}i&'5dichloro-phenylimine)-pyrro1idine minute in this preparation of the given active compound. Concentra- After immersion of, in each case, 10 female specimens of Inhlbltm aetlve of egg the various strains of ticks, the individual ticks are transcompound depositing ferred to plastic dishes, the bottom of each of which is 10 ParasteiBwphdm mwmplm m Percent Percent covered with a disc of filter paper. As a control, similar Ridgeland strain resistant 1.0 10 ticks of a normally sensitive strain are treated in exactly 3:? $3 the same manner. 3.3% 53 After 35 days, the eifectiveness of the preparation of the given active compound is determined by ascertaining 3mm mam resistant kg g? the inhibition of the depositing of fertile eggs compared 011 100 with the egg depositing of untreated control ticks. The 8:3? 8 elfect is stated in percent, 100% meaning that fertile eggs N n t 0 ceased to be deposited, and 0% signifying that the ticks 0mm yams was mm ,1 {33 have deposited eggs in normal manner like the untreated 100 0. 03 control ticks. 0.01

The following Tables 1a and 1b demonstrate the ovi- TABLE 1b.IN-V'ITRO TEST FOR OVICIDAL EFFECT ON TICKS Ovlcidal efiect against Boophilus, Biarra strain %inhibition with the stated 50%inhiconcentration bition active (percent by Active compound Physical constant compound weight) (2 01 B.P. 146-150 C.f0.6 mm. Hg 0.1 0. 01

c1 B.P. -469 (3.10.6 mm. Hg 0. 3 o. 1

l CI 02115 (41) B.P. lee-174 0.10.4 mm. Hg 0.03 0.01

( 21 JH2-CH=CHz (5;) B.P. 174-177" 0.11.7 mm. Hg 0.1 0.03

C1-N=\N/CHI (61) 13.1. 175-179" 0.10.8 mm.- Hg 0. ea 0.01

1 (Bl n-OaH1 (7 B.P. 179-184" (1/0.? mm. Hg 0.03 0.01

l Cl n-( hHa (8;) B.P. 165-170 0.10.6 mm. Hg 0.3 0.1

N l l C1 C2H5 (0|) O1 B.P. 152-157" 0.10.3 mm; Hg 0. 0a 0.01

TABLE 1b.I- N-YI'1RO '1EST FOR dvicmAL EFFECT ON '1ICK8--Continued I v Ovicidal efleet against Boophllus, Biarra strain 100% inhibition with the stated 50% inhiv concentration bition 5 I z ofactive (percent by Active compound Ph ysica1 constant compound weight) OH: B.P. 157-162 C./0.5 mm. Hg 0,1 0. 05

C1 N- J N 1 CH; (glib-CH1 CHI (1h) 13.1. 169-171 C-IOA mm. Hg 0.1 0.03

J N CH: 61 Hr-CH (12 3.1. 166-170" C-IOJS mm. Hg 0. 1 0. 03

All Ha-CH-CH:

(131 c1 7 3.1 180-184 0.11.5511. Hg 0.03 0. 01

All (311;

(14;) CE; 3.1. Mil-157 C.I1.3 mm. Hg 0. 3 0, 1

(15 OH: 13.1. INS- C./0.5 mm. Hg 0.3 0.1

nihHl (16 Cl -B.P. MES-162 C.l0.5 mm. Hg 0.03 0.01

13.1. 154-156 C-/0.B mm. Hg 0. 1 0. 03

(18 C1 B1. 162 18 4 CL/M mm. Hg 011. 7 0.1

-QA J (191) Bl. 165-173" C.I1.1 mm. Hg 0.3 0,17

(20 B.P. WIS-178 C;l1.5 mm. Hg 0. 8 0.1

TABLE lbw-INVITED TEST FOR OVICIDAL EF'EEGTQN Tmxsqontinu d Ovicidal oflect against Boophilus, Bum strain 1 mm ai 'z s W. m

6 S 8 B n concentration 'imltion 0! active (peroont by Active compound 7 Physical constant compound weight) 21 1 0H. r B.P. 153-151 QJOJ-mm. Hg -o.1 1 --o.oa

!1-&|H1 I 22, 01 3.1% 158-160 0.11.5 mm. H 0.1 0.0:

C1 N=\N/ JHz-CH-CH 23 on, 3.1. 143-141 c./1.s mm. Hg 0.3 .0:

'XGHOL I (241) cm B.P.153-167 C./1.0mm.Hg -1.o

(JHz-CH-CH l Ridgeland strain.

EXAMPLE 2 The following results were also obtained for further 4 tests carried out in accordance with Example 1. 0

TABLE z-m-vrrno TEST FOR OVICIDAL EFFECT ON TIOKS Ovicida! mm against Boophilns, Biarm strain 100% Inhibition with the stated 507 Inhiconcentration ifition of active (percent by Aetivo compound Physical constant compound 7 weight) (Z5|)-..-'..:;:.':;:.:: 3.1. 163-165 0.10.3 Hg 0. 1 0. 03

B: -Q l n. (2e1)....========= Br 3.2. nos-170 (1403mm Hg 1 0.1 0.05 -QA AHIGH=CHQ TABLE 2.-1N-v1'rRo 'rE s'r FQB oyrorna-n EFEEGT-ON TlGKscontlpued j;

. it r r V -r ,M.ofimafifiefigfihsf, Boophilus, Biarra strain 100%inhibition with the stated 50% inhiconcentration bition I of active (percent by Actlve compound v .Physicalconstant compound vreight) 13.1.- 15Q-1 M C./0.oti t-1"" as" 1.".."1 Q I'. Y Br J N 1 (JaH 41,) 'B.P.155-1'58 0.10.01mm. Hg m 0.1

Br- N= J G \N 271 lHa-CH=CH2 (421) B-JP. firs-160 04001 mm. Hg as V 0.2

Br N= J G \N ()1 n-CHl (4aI) on Y B;1 ".ii5 152-'@./o.mmm.11g 0.1 0.03

N JIHg-CH- -CH (On-13224.2 01H 1 BE. 143-i52 C./0.01 mm. Hg I 0.3 0:1

Br N:

Hz-CH=GH:

(find-3217..."; B1 B1. 15646? (LN-2 mm. Hg Orl Q1 JH -CH=GHz (4e)-.- 2 CH; 15.1. 151-161 C.l0.2mm.Hg v .3 0.2

N n-rH! (471)": 3.1. 149-154" 0.10.03 mm. Hg 0. 1 0.08

F Ni 1 Bl H:CH=CH1 EXAMPLE 3 In-vivo test against ticks on cattle with 7 parts of a mixture of equal parts by Weight of ethyleneglycol monomethyl ether and nonylphenyl polyglycol ether. The emulsion concentrate so obtained is diluted with water to the application concentration desired in each case.

7 Cattle which have been infected (12 timesatintervals of 2 days) with resistant larvae of ticks of the species Boophilus microplus, Biarra strain, are sprayed on the 24th day after the first infection with the preparation of the glvtm active compound so obtained.

The efiect of the preparation of the given active compound is determinedby ascertaining the number of adult female ticks which have reached development on the .1 treated cattle and later la viable e This number is 3 parts of the particular active compound are mixed65 y ggs In-vitro test for ovicidal and adulticid-al effect on ticks reached development on untreatedcattle. The more effective a compound; the fewer female ticks which reach development after treatment and lay viable eggs.

As a measure of the intensity of the infestation before 0 treatment, there is used the number of adult females which reach development in the case of the treated and untreated animals in the last three days before the time of treatment. a I

The particular active compounds tested and the results 76 obtained can be seen from the following Table 3.

TABLE 4.-IN-VITRO TEST FOR OVICIDAL AND ADULTICIDAL EFFECT ON TIOKB-Continued Adultlcidal and ovlcldal ofloct afiainst Boophilus, B one strain 1007 507 Active compound Physical constant inhibition inhibition (631) m B.P. 171-176 0.10.? mm. Hg 0. 1 0.03

-Q- i l l f 01 CHzCH=GH-CH:

(64 C1 B.P. 173177 C./0.5 mm. Hg 0.01 0.03

Not adultlcidal 01 N- f GHQ-C H.=C H-CH:

(65 (31H; B.P. 161-167 0.10.3 mm. Hg 0. 1 0. 05

Not adulticldal Br N OHz-CH=(JH-CH:

(661) CH; B.P. 155162 C./0.3 mm. Hg 0. 03 0.02

Not adulticidal 01 N N l CHIC H=C H5 (671) CH; B.P. 156161 C./0.2 mm. Hg 0. 03 0. 02

CHQCH=CHI (681) Cl B.P. 162-166 C./0.8 mm. Hg 0. 03 0. 0

CH -C H=CH| 1 With the stated concentration of active compound in percent by weight.

EXAMPLE 5 50 The results below were obtained in a similar manner to those in accordance with Example 4.

TABLE 5.-IN-VITRO TEST FOR OVICIDAL AND ADULTICIDAL EFFECT ON 'IICKS Adulticidal and ovicidal efiect against Boophilus,

Active compound Physical constant Elana strain 1 507 inmbm fi inhibition D B.P. 174-179 0.10.5 mm. Hg

f CHI CH=CH-CH1 B.P. 159-166" C./0.5 mm. Hg

B.P. Mil-167 040.5 mm. Hg

TABLE 5.IN-VITRO TEST FOR OVICIDAL AND ADULTICIDAL EFFECT ON TICKS-Continued Active compound 1 With the stated concentration of active compound in percent by weight.

EXAMPLE 6 l CHr- C H=CH1 60 g. 2,4-dichloro-aniline and 51 g. N-allyl-pyrrolidone- (2) are dissolved in 300 g. toluene, and 53 g. phosphorus oxychloride are added dropwise. The mixture is then heated under reflux until evolution of hydrogen chloride has ended (34 hours). The mixture upon cooling is poured into ice water and excess solution of sodium hydroxide, and the toluene solution is dried over potassium carbonate and fractionally distilled. An oil, B.P. 160- 164/0.8 mm. Hg, is obtained. Yield: 82 g. of 1-(a-allyl)- 2-(2,4'-dichloro-phenylimino)-pyrrolidine.

The toxicity determined on the mouse is: orally, 500 mg./kg.; subcutaneously, 500 mg./kg. (highest survived doses).

All of the other compounds of the present invention are prepared in the same manner, as the artisan will appreciate. For example, the following compounds are produced in a similar manner:

1-ethyl-2-(2',4', '-trichloro-phenylimino)-pyrrolidine,

1-ethyl-2 (3',4'-dichloro-phenylimino)-pyrrolidine,

1-tert.-butyl-2-(2'-methy1-4'-chloro-phenylimino)- pyrrolidine,

1- (a-allyl) -2- 2',4-dibromo-phenylimino) -pyrrolidine;

and

pyrrolidine.

It will be realized that all of the foregoing compounds contemplated by the present invention possess the desired selective pesticidal, especially parasiticidal, i.e. animal acarid ectoparasiticidal, properties for combating parasites, especially animal acarid ectoparasites, and that such compounds have only a very slight toxicity toward warmblooded creatures.

It will be appreciated that the instant specification and examples are set forth by way of illustration and not limitation, and that various modifications and changes may be made without departing from the spirit and scope of the present invention.

What is claimed is:

1. The method of combating animal acarid ectoparasites which comprises applying to at least one of (a) such ectoparasites and (b) their animal habitat an ectoparasiticidally efiective amount of a 2-phenyliminopyrrolidine of the formula Physical constant 18.1. 163168 C./0.4 mm. Hg

507 inhibition inhibition l in which R is selected from the group consisting of chloro, bromo, fluoro and alkyl of 1-4 carbon atoms, n is a whole number from 2-3, with the proviso that at least one of the substituents R is selected from the group consisting of chloro, bromo and fluoro, R is alkenyl of 3-4 carbon atoms, and R" is selected from the group consisting of hydrogen and alkyl of 1-4 carbon atoms.

2. The method of claim 1 wherein R is selected from the group consisting of chloro, bromo, fluoro and C alkyl, n is a Whole number from 2-3, with the proviso that at least one of the substituents R is selected from the group consisting of chloro, bromo and fluoro, and R" is selected from the group consisting of hydrogen and C1 2 alkyl.

3. The method of claim 1 wherein R is selected from the group consisting of dichloro, trichloro, dibromo, (C alkyl)-(chloro), (C alkyl)-bromo), chloro-bromo, chloro-fluoro and bromo-fluoro, and R" is selected from the group consisting of hydrogen and C alkyl.

4. The method of claim 1 wherein R is selected from the group consisting of 2,3-, 2,4-, 2,5- and 3,4-dichloro, 2,4,5-trichloro, 2,4- and 3,4-dibromo, 2-chloro-4-bromo, 2-bromo-4-chloro, 3-chloro-4-bromo, 3-bromo-4-chloro, 3-chloro-4-fluoro, 2-chloro-4-fiuoro, 2-methyl-4-chloro, 3-methyl-4-chloro, 3-chloro-4-methyl, 2 bromo 4-fluoro, 3-bromo-4-fluoro,2-methyl-4-bromo, and 2-ethyl-4-bromo, and R" is selected from the group consisting of hydrogen and C alkyl.

5. The method of claim 1 wherein such compound is ('3H CH=CH; 6. The method of claim 1 wherein such compound is lNJ ALBERT T. MEYERS, Primary Examiner F. E. WADDELL, Assistant Examiner 22 3-3 um'rmn s'rA'ms m rmr omen CERflIFICATE CF CORRECTION Patent No. 7 Dated January 22, 1974 nwemorm EDGAR ENDERS ET AL page 1 It is certified that error appears in the aboye-identified patent and that said Letters Patent-are hereby corrected as shown below:

Col. 8, Table la, in 'the last column of Table, under 50" insert 0 Col. 9, Table lb, Compound (12 correct formula to read as follows:

, .020 .I n CIQ iNJ l I ca es-c11 Col. 9, Table lb, Compound (1 8 in the thri'd column of the Table, change "0.1" to 0.3

Col. 11, Table lb, Compound (22 correct formula to read as follows:

Col. 11, Table lb, Compound (24 correct formula to read as follows UNITED STATES PATENT OFFICE Page 2 CERTIFICATE OF CORRECTION Inventor(s) Edgar Enders et a1.

It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Col. 16, line 65, cancel In-vitro... .....i.ticks" and substitute therefor compared with the number p of adult female ticks which have Col. 17, Table 3, in the title of Table, cancel "VITRO" and substitute therefor VIVO "Q Col. 18,, Table A, Compound (49 in thelast column ofTable,

change "0.30" to" 0.03

Cols. 21-22, Table 4, Compound (68 correct formula to read as follows:

- 4 H10 N NJ v last column of Table, after "0.0", insert l Signed and sealed this 18th day of March 1975.

Attest:

' RUTH C. MASON Commissioner of Patents Attesting Officer and Trademarks 

